FRMD8抑制肺癌细胞的增殖与迁移

FRMD8 inhibits amplification and migration of lung cancer cells

目的探讨FERM domain-containing protein 8(FRMD8)在肺癌发生发展中的作用。方法用Western blotting检测肺癌组织及相应癌旁正常组织中FRMD8的表达情况;敲低FRMD8后平板克隆形成实验检测细胞克隆形成能力,MTT法检测细胞增殖情况;过表达FRMD8后流式细胞术检测细胞凋亡情况,Western blotting检测过表达FRMD8后某些细凋亡相关蛋白表达变化;过表达及敲低FRMD8后Transwell细胞迁移实验检测对A549细胞迁移能力的影响。结果 1.与正常组织相比,肺癌组织中FRMD8表达下调(P<0.05);2.FRMD8敲低,细胞克隆形成能力及增殖速度提高;3.FRMD8可诱导细胞凋亡,并影响细胞凋亡相关基因的表达或活化:FRMD8过表达可下调Caspase-3、8和bax表达,而p53、激活型Caspase-3、8以及bcl-2的表达上调;4.FRMD8过表达抑制细胞迁移能力(P<0.01),而敲低FRMD8则促进细胞迁移(P<0.001)。结论 FRMD8可抑制肺癌的发生发展,并具有肿瘤抑制子的功能。

Objective To investigate the role of FERM domain-containing protein 8（ FRMD8） in lung cancer progression,and explore the mechanism. Methods Western blotting was used to detect expression of FRMD8 in 14 pairs of matched non-involved lung tissue and lung cancer tissues; Colony formation assay and MTT assay were performed for detecting cell proliferation after A549 cells were transfected with siRNAs. Flow cytometry / FACS was applied to detect apoptosis of A549 cells after FRMD8 being up-regulated,Expression of apoptosis-related proteins was evaluated by Western blotting following FRMD8 was up-regulated. A549 cells were transiently transfected with siRNAs or FRMD8 expression vectors,then Transwell migration assay was carried out to test the influence of FRMD8 on cell migration. Results 1.Compared with normal tissues,FRMD8 expression in lung cancer tissues was down-regulated significantly（ P〈0. 05）; 2.Colony formation and MTT assay showed that inhibition of FRMD8 expression by siRNAs promoted proliferation of A549cells; 3. Over-expression of FRMD8 induced apoptosis and regulated expression of apoptosis-related proteins： Caspase-3,Caspase-8 and Bax were down-regulated,and cleaved Caspase-3,Caspase-8 and bcl-2,p53 were up-regulated; 4. Downregulation of FRMD8 promoted migration（ P〈0. 01）. Over-expression of FRMD8 repressed migration of A549 cells（ P 〈0. 001）. Conclusion FRMD8 represses lung cancer progression and may act as a tumor repressor.